Evaluation of hydroperoxides in common pharmaceutical excipients

摘要: While the physical properties of pharmaceutical excipients have been well characterized, impurities that may influence chemical stability formulated drug product not studied. In this work, hydroperoxide (HPO) impurity levels common are measured and presented for both soluble insoluble excipients. Povidone, polysorbate 80 (PS80), polyethylene glycol (PEG) 400, hydroxypropyl cellulose (HPC) were found to contain substantial concentrations HPOs with significant lot-to-lot manufacturer-to-manufacturer variation. Much lower HPO in fillers, like microcrystalline lactose, high molecular weight PEG, medium chain glyceride (MCG), poloxamer. The findings discussed within context HPO-mediated oxidation formulating substance sensitive oxidation. Of four levels, povidone, PEG HPC a mixture hydrogen peroxide organic while PS80 contains predominantly HPOs. implications these respect known manufacturing processes chemistry reactivity degradation kinetics. Defining critical limits should be driven by specific or can only defined context.